Cocaine abuse remains a major public health problem with as yet no definitive behavioral or pharmacologic approach for its treatment.This may relate to the heterogeneity of the population. This application comprehensively addresses one possible subgroup, cocaine abusers with adult attention deficit hyperactivity disorder (ADHD). This group may represent a significant minority of cocaine abusers who may be responding differently to cocaine. Since estimates of this group have ranged from 5- 35% of treatment seekers, we propose to do a comprehensive diagnostic study of this disorder in three ethnically different cocaine abuse treatment-seeking populations to shed additional light on the prevalence of this disorder. At the same time, we will be carrying out a double- blind, placebo-controlled study using two medications that have been found useful to treat ADHD in adolescence (methylphenidate and desipramine). The twelve-week outpatient trial will look at the efficacy of these medications combined with a manual-controlled relapse prevention method using treatment retention, cocaine use and cocaine craving, and reduction of ADHD symptoms as major outcomes. A six-month follow-up will be done to assess the stability of any changes. Clinical reports have suggested that some cocaine abusers with ADHD have a paradoxical reaction to cocaine, similar to the effect that adolescents with this disorder have when they take stimulants. However, no laboratory studies have been done to substantiate this observation. A unique aspect of this grant proposal will be our ability to directly compare, under controlled laboratory conditions, the subjective and physiologic effects of acute cocaine doses, as well as the choice/self-administration of cocaine (versus a non-drug option), in cocaine abusers, with and without ADHD. Additionally, the effects of methylphenidate and desipramine pretreatment on these responses will also be addressed in the laboratory. This combination of novel treatment strategies, innovative laboratory investigations, and epidemiologic studies should significantly advance our knowledge of a potentially important subgroup of cocaine abusers, and aid in important medication development efforts for the treatment of cocaine abuse.